In the vertebrate retina, two distinct lateral inhibitory mechanisms contribute to the shaping of ganglion cell responses and their receptive field organization. Sustained lateral inhibition is activated by steady illumination and transient lateral inhibition by stimuli that are changing in intensity or are moving. These lateral inhibitory mechanisms are mediated by separate synaptic pathways in the retina. Both mechanisms undergo significant, but different, changes between light- and dark- adapted conditions. The proposed research will investigate the synaptic pathways involved in each of these two lateral inhibitory mechanisms and how they are modulated during changes in the state of adaptation. Intracellular recordings will be made from ganglion cells in intact retinas in superfused eyecup preparations from the tiger salamander, a well-studied animal model of the vertebrate retina. Ganglion cell responses to illumination of different parts of the receptive field with various stationary and moving light stimuli will be made under different conditions of adaptations. Pharmacological treatments with agonists and antagonists to specific neurotransmitters, drugs which block action potential generation, and putative neuromodulator substances will be used to dissect the contributions of different synaptic pathways to components are modulated by light adaptation. These studies should contribute to our understanding of visual information processing in the retina and how the synaptic pathways are modulated during light and dark adaptation to optimize the output of retinal ganglion cells for differing visual conditions.